Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers.
Clin Pharmacol TherJul 14, 2026 (epub)
Sidharth Anand, Nicholas A Buckley, Paul Stathakis et al.
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In 30 seconds
This randomized crossover study evaluated the effects of fomepizole on NAPQI formation in healthy volunteers after acetaminophen overdose. Administered 2 hours post-ingestion, fomepizole significantly reduced urinary NAPQI metabolites by 60-70% for both immediate-release and modified-release acetaminophen, indicating its potential as an adjunct treatment in acetaminophen overdose scenarios.
Key findings
- Fomepizole reduced urinary NAPQI metabolites for immediate-release acetaminophen from 4.92% to 1.72%.
- For modified-release acetaminophen, urinary NAPQI metabolites decreased from 5.62% to 1.43% with fomepizole.
- Mean serum NAPQI metabolite AUCs were significantly lower with fomepizole for both formulations, indicating reduced toxicity.
Why it matters
The findings suggest that fomepizole may be a valuable adjunct therapy in acetaminophen overdose, particularly when acetylcysteine treatment is delayed or inadequate, potentially improving patient outcomes in emergency settings.